PP.31.04] INVOLVEMENT OF RENIN-ANGIOTENSIN SYSTEM IN MONOCROTALINE INDUCED PULMONARY HYPERTENSION

Abstract

Objective: Pulmonary arterial hypertension (PAH) is a rare and complex disease, where renin-angiotensin system (RAS) is known to be activated. Monocrotaline induced PAH is well known experimental animal model. We aimed to measure RAS components, including angiotensin converting enzyme (ACE) and its receptors in various tissues. Additionally, we hypothesized, that kidneys might pose as a source of RAS activation, as they excrete renin, which is a rate limiting step of angiotensin II formation. Design and method: Group of 15 male Wistar rats was injected with monocrotaline (60 mg/kg) and 7 control rats (CON) received vehicle. Separate group of 20 (MCT) and 10 (CON) rats was used for hemodynamic measurements. Animals were weighted frequently and vital functions were measured using MouseOx meter. Rats were sacrificed after 4 weeks or immediately if showing dyspnea, lethargy and significant weight loss. Results: MCT-treated rats exhibited significant increase in the right ventricular systolic pressure (MCT: 50.65 ± 6.28 vs. CON: 21.52 ± 2.49, P < 0.01). Right ventricular (RV) weight was significantly increased (MCT: 0.29 ± 0.02 vs. CON: 0.17 ± 0.01, P < 0.05), whereas left ventricular (LV) weight was not significantly changed (MCT: 0.69 ± 0.03 vs. CON: 0.70 ± 0.05). Expression of ACE mRNA was significantly increased in the RV (MCT: 2.31 ± 0.41 vs. CON: 1.00 ± 0.16, P < 0.05), also in the LV (MCT: 2.37 ± 0.26 vs. CON: 1.00 ± 0.06, P < 0.01), as was in the kidney (MCT: 1.66 ± 0.25 vs. CON: 1.00 ± 0.15, P < 0.05), but in lungs was significantly decreased (MCT: 0.47 ± 0.03 vs. CON: 1.00 ± 0.06, P < 0.01). Expression of angiotensin II receptor type 1 was significantly increased in the RV (MCT: 2.1 ± 0.21 vs. CON: 1.00 ± 0.13, P < 0.05), while in the left ventricle, lungs and kidney was unchanged. There was no significant alteration in the mRNA of angiotensin II receptor type 2 in the heart, lungs or kidney. Renin mRNA expression was significantly increased in the kidney (MCT: 2.46 ± 0.69 vs. CON: 1.00 ± 0.13, P < 0.01). Conclusions: Renin-angiotensin system is activated in the heart and kidneys, for which the increased kidney renin might be responsible. Interestingly, the opposite effect is present in lungs, where ACE is decreased.